The aetiology and pathophysiology of non-union is still unclear, but in this condition there is an abnormal bone metabolism. The paracrine matrix RAS has been implicated in the regulation of bone remodeling and injury responses, possibly via its effects on kinins. The influence of the local RAS or the genetic influence of the ACE/ BK2R genes to bone remodelling may thus be central to the disorder, or augmented in these conditions. We thus compared the distribution of the ACE I/D and BK2R “+9/-9” functional polymorphisms in patients with non-union and compared them to appropriate control. Gene analysis was performed on buccal cells collected from all subjects and the data was analysed for 59 patients (46 males, 13 females; mean age 40.1±15.7 years) with non-union and 81 control subjects (49 males, 32 females; mean age 51.4±22.81 years. The overall genotype distribution was consistent with Hardy-Wein-berg equilibrium for the overall and individual groups for ACE ( As the -9 allele is associated with greater gene transcription and higher mRNA expression of the receptor we combined the -9/-9 homozygous and -9/+9 heterozygous groups and compared them with the homozygous +9/+9 groups. This showed a significant difference between the non-union and control groups, with the +9/+9 homozygous being less prominent in the former ( The B2BKR -9 allele is associated with the incidence of non-union in fracture healing, in this first study to address this question. We found no association with either the In conclusion, with previous findings that the absence of the -9 allele of the B2BKR +9/-9 polymorphism is associated with greater gene transcription and higher mRNA expression of the receptor our findings are suggestive that increased BK activity via the B2BKR may predispose to the development of non-union.
Drug therapy forms an integral part of the management
of many orthopaedic conditions. However, many medicines can produce
serious adverse reactions if prescribed inappropriately, either
alone or in combination with other drugs. Often these hazards are
not appreciated. In response to this, the European Union recently
issued legislation regarding safety measures which member states
must adopt to minimise the risk of errors of medication. In March 2014 the Medicines and Healthcare products Regulatory
Agency and NHS England released a Patient Safety Alert initiative
focussed on errors of medication. There have been similar initiatives
in the United States under the auspices of The National Coordinating
Council for Medication Error and The Joint Commission on the Accreditation
of Healthcare Organizations. These initiatives have highlighted
the importance of informing and educating clinicians. Here, we discuss common drug interactions and contra-indications
in orthopaedic practice. This is germane to safe and effective clinical
care. Cite this article:
A 48-year old man presented with back pain that was resistant to treatment. An MR scan showed spondylolisthesis at L4-5 and narrowing of the exit foraminae. He had a posterior fusion which did not relieve his symptoms. He continued to have back pain and developed subcutaneous nodules in both forearms. Biopsy from the skin revealed cutaneous sarcoidosis, and one from the lumbar spine showed sarcoidosis granuloma between the bone trabeculae. A CT scan of the abdomen and chest revealed axillary lymphadenopathy, mediastinal enlarged nodes, apical nodular nodes and splenomegaly. The patient was started on large doses of methotrexate and steroids. His angiotensin-converting enzyme and calcium levels returned to normal and the back pain resolved.
